Disease relevance of Pap

• We tested this hypothesis by screening by RT-PCR reactions the expression of the PAP/HIP gene in several human pituitary adenomas, especially GH-producing adenomas [1].
• Expression of peptide-23/pancreatitis-associated protein and Reg genes in human pituitary and adenomas: comparison with other fetal and adult human tissues [1].
• In the rat, three isoforms of PAP are known, all of which are upregulated during acute pancreatitis [2].
• Pseudomonas pneumonia-mediated sepsis induces expression of pancreatitis-associated protein-I in rat pancreas [3].
• Role of platelet-activating factor in pancreatitis-associated acute lung injury in the rat [4].

High impact information on Pap

• During development, Reg-2 production by motor and sensory neurons is regulated by contact with peripheral targets [5].
• Axon-stimulated Schwann cell proliferation is necessary for successful regeneration, and we show that Reg-2 is a potent Schwann cell mitogen in vitro [5].
• Thus, Reg-2 is a neurotrophic factor for motoneurons, and is itself an obligatory intermediate in the survival signalling pathway of CNTF-related cytokines [6].
• Reg-2 shows a unique pattern of expression in late embryonic spinal cord: it is progressively upregulated in individual motoneurons on a cell-by-cell basis, indicating that only a fraction of motoneurons in a given motor pool may be exposed to cytokines [6].
• BACKGROUND & AIMS: In pancreatitis-associated lung injury, neutrophils (PMN) access the lung by migration through endothelial basement membranes [7].

Chemical compound and disease context of Pap

• Treatment with lexipafant 30 min and 6h after pancreatitis reduced severity of pancreatitis-associated intestinal dysfunction, associated with a diminish in systemic concentrations of IL-1 and local leukocyte recruitment [8].
• In sodium deoxycholate-induced pancreatitis, the levels of TGF-beta1 were also elevated in the plasma (9.2 +/- 0.8 ng/mL), in the pancreatitis-associated ascitic fluid (11.5 +/- 0.6 ng/mL), and in the liver homogenate (2.8 +/- 0.3 ng/g of liver tissue) [9].
• Platelet-activating factor (PAF) may play a critical and primary role in the pathogenesis of acute pancreatitis and pancreatitis-associated distant organ injury [10].
• Inosine alleviates rat caerulein pancreatitis and pancreatitis-associated lung injury [11].
• Our observations indicate that PGE1 reduces the severity of pancreatitis-associated acute lung injury by preventing neutrophil sequestration within the lung [12].

Biological context of Pap

• Pancreatic stone protein (PSP/reg), which shows strong sequence homology to PAP, is secreted into pancreatic juice under physiologic and pathologic conditions [2].
• The deduced amino acid sequence revealed that PAP was synthetized as a preprotein with, in its mature form, a predicted molecular weight of 16,630 [13].
• Messenger RNA sequence and expression of rat pancreatitis-associated protein, a lectin-related protein overexpressed during acute experimental pancreatitis [13].
• The PAP coding sequence spanned over six exons [14].
• The rat PAP gene was isolated from a genomic library and characterized over 3.2 kilobases of gene sequence and 1.2 kilobases of 5'-flanking sequence [14].

Anatomical context of Pap

• Our results show a weak expression of the PAP/HIP gene in the pituitary gland and in most of the tumors, but independent of their origin [1].
• In situ hybridization was used to localize peptide-23/PSP in the small intestine and pancreas of GRF-treated rats [15].
• Both peptide-23/PAP and PSP/reg mRNA levels in duodenum and jejunum were increased in these rats compared with levels in control rats [15].
• These data demonstrate that GRF modulates peptide-23/PAP expression in the gastrointestinal tract in a similar fashion to that previously reported for pituitary cells in primary culture [15].
• PAP mRNA could not be evidenced in liver, stomach, salivary glands, brain, kidney, or testis [13].

Associations of Pap with chemical compounds

• By means of the mixed oligonucleotide-primed amplification of cDNA technique, primers corresponding to the NH2-amino acid sequence of peptide 23 were used to amplify, clone, and sequence a 74-basepair cDNA of peptide 23 [16].
• Expression of pituitary peptide 23 in the rat uterus: regulation by estradiol [17].
• A single injection of 17 beta-estradiol resulted in a transient induction of peptide 23/PAP mRNA in ovariectomized rats whereas a sustained induction was seen with diethylstilbestrol implants [17].
• In situ hybridization localized peptide 23/PAP mRNA to the luminal epithelial cells [17].
• Tumor necrosis factor alpha triggers antiapoptotic mechanisms in rat pancreatic cells through pancreatitis-associated protein I activation [18].

Regulatory relationships of Pap

• The secretion of peptide 23 by rat pituitary cells is stimulated by growth hormone-releasing hormone and inhibited by somatostatin [19].
• However, by 7 d after axotomy, Reg-2 is expressed in medium to large neurons and coexists partly with the neuropeptides galanin and neuropeptide Y, which are also upregulated after peripheral nerve transection [20].

Other interactions of Pap

• We then extended our work to normal adults and developing human tissues to compare the expression patterns of the PAP/Reg gene family [1].
• RESULTS: Analysis of the open reading frame of the cDNA indicated that the deduced protein from the messenger RNA (mRNA) was a polypeptide of 174 amino acids, unexpectedly similar to that of a known gene, rat pancreatitis-associated protein II/regenerating gene III (PAP II/Reg III) [21].
• Furthermore, pretreatment with a selective ETA receptor antagonist (1 microg/kg body wt) almost abolished pancreatitis-associated capillary constriction, restored functional capillary density, and, consequently, improved overall nutritive perfusion [22].
• ETA and ETB receptor function in pancreatitis-associated microcirculatory failure, inflammation, and parenchymal injury [22].
• We used Western blot and immunohistochemical methods to investigate the biochemical characteristics and cellular distribution of a novel peptide (peptide 23) that was previously shown to be released from anterior pituitary cells of rat in response to growth hormone-releasing hormone [23].

Analytical, diagnostic and therapeutic context of Pap

• Double immunofluorescence for PSP/reg and PAP I or II demonstrates that these proteins colocalize to the same cell [24].
• RNA was extracted for Northern blot analysis of PAP I, II, and III and PSP/reg mRNA [25].
• RNA amplification by reverse-transcriptase-coupled polymerase chain reaction showed that PAP mRNA was constitutively expressed in duodenum, jejunum, and ileum, at similar levels as in pancreas during the acute phase of pancreatitis [14].
• Molecular cloning and expression of peptide 23, a growth hormone-releasing hormone-inducible pituitary protein [16].
• Among these five family members, the expression of Reg-2/PAP I mRNA was predominantly enhanced in injured motor neurons after axotomy [26].

References